TEL AVIV, ISRAEL—Physicians for decades have grappled with ways to block further tissue damage in patients who suffer heart attacks. They have tried everything from drugs to cell therapy—all with little luck. But promising new research indicates that a biogel made from seaweed may have the healing powers that have thus far eluded them.

The first clinical trial in humans recently began of an alginate-based biomaterial that, when injected into animals, helped their hearts repair themselves. The therapy is set to be tested over the next year in 30 patients in Germany, Belgium and Israel who have suffered severe heart attacks; if successful, the trial will be expanded to include a few hundred U.S. heart patients, and the experimental biogel could be on the market by 2011.

A heart attack, or myocardial infarction, occurs when blood flow to the heart is cut off, killing part of the muscle due to lack of oxygen. The severity of the damage depends on the amount of time that elapses before blood flow is restored. Once damaged, heart tissue never regenerates; if a patient survives, necrotic (dead) tissue is replaced by scar tissue.

The scar wall is thinner than that of surrounding healthy tissue. Damage to the region worsens and spreads when inflammatory cells (that rush to the scene as part of the body's immune response) secrete enzymes that erode the exposed extracellular matrix, the natural scaffolding that supports heart cells. As the scar gets larger, the wall gets thinner.

To compensate, the remaining healthy muscle works harder to pump blood, swelling as it does so. For about 10 to 20 percent of heart attack survivors, this overexertion may lead to arrhythmia (irregular heartbeat), future heart attacks, heart failure and even death, according to Leor.

Leor has spent the past fifteen years researching potential ways to prevent this deterioration. He initially tested therapies incorporating stem cells, which he thought might spawn new heart cells or prompt hobbled hearts to regenerate their own. The results were disappointing: most of the stem cells died, and those that survived failed to spur new tissue growth.

He says he then discovered that the damage was related to the extracellular matrix. That is, the progressive thinning of the scaffolding put a strain on the healthy areas of the heart. Rebuilding this support would not only give a boost to remaining muscle mass, he reasoned, but would also provide more real estate on which cells could live and replicate.

"I thought maybe we could prevent that [deterioration]" by using a biomaterial as a substitute for the lost natural tissue, Leor says.

At the same time, Smadar Cohen, head of the Department of Biotechnology Engineering at Ben-Gurion University of the Negev in Israel, was exploring the potential of a biomaterial to fix damaged hearts after having successfully used it to repair liver tissue.

Cohen wanted to design an implant on which cells replicated by surrounding healthy tissue could set up shop; she believed that once there, the cells would excrete extracellular material that would thicken scar tissue as well as prevent its expansion. She initially considered using polymers (large molecules comprising repeating units) made of natural human proteins such as collagen or synthetic ones made from degradable polyester. But neither material was up to the task, which prompted her to consider alginate, a seaweed-derived polymer, which has a similar molecular structure to natural extracellular material and has been used by the food, drug and medical-device industries.

Cohen froze the alginate solution to form water crystals, which she then flash-dried. The result was a porous substance on which cells could grow and link to one another. Cohen formed the material into a Band-Aid–like patch, which she applied directly to the hearts of rats (and later pigs) after inducing heart attacks.

Blood vessels grew into the patch, and heart cells from neighboring areas settled and reproduced on it, secreting their own extracellular material that beefed up the scar tissue. After six weeks, the alginate disintegrated and the remains were excreted in urine—leaving behind tissue in the rats and pigs that was significantly healthier than that in those that did not receive the implants. The problem was that the patch could only be inserted via risky open-heart surgery, limiting the likelihood of volunteers for human trials, Leor says.

In an effort to lower the risk, Cohen stitched the alginate polymers into an injectable solution that would turn into a sticky gel when it came into contact with calcium ions (the electrically charged form of calcium atoms that circulate in the bloodstream) that congregate at the site of heart muscle damage.

The gel proved so promising in rats that in 2005, BioLineRx, Ltd., an Israeli start-up created to bring promising early-stage therapies to clinical trials, selected Cohen's process from among hundreds of potential treatments. It continued to test the biogel, which it dubbed BL-1040, in pigs (which are anatomically similar to humans)—with the same success as Cohen had with the patch.

Leor says that no negative side effects were observed. But he notes the results may have been skewed, because the animals were young and healthy (until researchers induced their heart woes), whereas most heart attack victims are elderly and have other diseases and complications. "The challenge,'' he says, "is to show that our approach will be effective in real patients."

Timothy Gardner, president-elect of the American Heart Association and medical director of the Center for Heart & Vascular Health at Delaware's Christiana Care Health System, is cautiously optimistic. "This addresses a real problem, and if [the human trials] are successful," he says, "it will be an important additional therapeutic option."

ABOUT THE AUTHOR(S)

Cynthia Graber

Cynthia Graber is a print and radio journalist who covers science, technology, agriculture, and any other stories in the U.S. or abroad that catch her fancy. She's won a number of national awards for her radio documentaries, including the AAAS Kavli Science Journalism Award, and is the co-host of the food science podcast Gastropod. She was a Knight Science Journalism fellow at MIT.

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